Human natural killer (NK) cells and K cells mediating antibody-dependent cellular cytotoxicity have been shown to be large granular lymphocytes (LGL). The majority of LGL form lytic conjugates with a large variety of NK-susceptible target cells. Interferon caused augmentation of NK and K cell activities of LGL and only LGL demonstrated either spontaneous or interferon-activated NK activity. The mechanism of augmentation by IFN appeared to be multiple: 1) increase in lytic efficiency, 2) increase in lytic binders, 3) increase in number of binders, and 4) increased recycling of effector cells. Natural, recombinant and hybrid recombinant alpha interferon molecules have all been shown to augment NK activity but vary widely in their potency relative to antiviral activity. Activation of one of the interferon metabolic pathways with macromolecular substrates (2'-5')pppApApA resulted in increased NK activity. Cultures of highly purified LGL in the presence of T cell growth factor demonstrated typical morphology and cytotoxic patterns of fresh NK cells. Subpopulations, cultures and clones of LGL (NK cells) are being studied against a variety of NK targets.